Nutrition, metabolism and lactation

Producing eggs or sperm, carrying a pregnancy and feeding a newborn all cost energy. It is therefore not surprising that the reproductive system listens closely to signals about nutrition and metabolism. Research in this area asks how the brain learns about the body’s energy reserves, why both too little and too much body fat can disturb fertility, how breastfeeding suppresses ovulation, and how the nutritional environment before birth may shape health decades later.

Energy reserves and the reproductive axis

Reproduction is controlled by a hormonal chain often called the reproductive axis: a part of the brain called the hypothalamus releases gonadotrophin-releasing hormone (GnRH) in pulses, which drives the pituitary gland to release the hormones that act on the ovaries or testes. Nutritional signals can act at the top of this chain.

An influential paper from 1974 examined girls and young women whose menstrual cycles had stopped after weight loss. Cycles returned after weight was regained, and the authors proposed that a minimum store of readily mobilised energy, reflected in body fatness, is needed for ovulation and for the onset and maintenance of menstrual cycles. The idea was striking but left open the question of how fat tissue could communicate with the brain.

Part of the answer came in the 1990s with the hormone leptin, produced by fat cells. Female mice of the ob/ob strain, which cannot make functional leptin, are obese and remain sterile even when dieted down to a normal weight, because their hypothalamus and pituitary do not produce enough reproductive hormone. A 1996 study showed that repeated injections of leptin alone restored ovulation, pregnancy and birth in these animals. The finding showed that a signal from fat tissue can act directly on the reproductive axis.

Obesity and fertility

At the other end of the scale, obesity has become a major theme of reproductive research, reflected in several of the more recent articles in the archive. According to a 2021 committee opinion of the American Society for Reproductive Medicine, obesity increases the risk of infertility, although most women and men with obesity are fertile. In women it is associated with ovulatory problems, a weaker response to drugs used to induce ovulation and lower birth rates after IVF, and it raises the risk of complications for mother and baby during pregnancy. Men with obesity may also show impaired reproductive function.

Researchers continue to study the mechanisms behind these associations, together with related questions such as how body weight relates to the timing of puberty in girls and boys, a theme also present in the archive.

Lactation and the pause in fertility

In most mammals, a mother who is suckling her young does not conceive again straight away. The controlling signal is suckling itself. In women, it is the only truly physiological signal known to suppress fertility in healthy, well-nourished mothers. In early lactation, the pulsatile release of GnRH and luteinising hormone is almost completely inhibited. Fertility then returns in stages: irregular hormone pulses and some follicle growth, then cycles in which follicles grow but ovulation often fails or the corpus luteum is inadequate, and finally normal ovulatory cycles.

How long this takes varies a great deal between women, a variation linked to the strength of the suckling stimulus in each mother–baby pair. Suckling appears to make the hypothalamus more sensitive to the suppressive effect of oestradiol, a mechanism that seems common across species, whereas the role of prolactin, the milk-production hormone, differs between species. The exact neural pathway from nipple stimulation to the GnRH pulse generator is still not fully understood. Field studies of wild primates and work on lactating farm and laboratory animals, both represented in the archive, have helped to show how widespread lactational anoestrus is.

Milk yield versus fertility in dairy cows

Farm animals provide a vivid example of the trade-off between lactation and reproduction. As milk production per cow has risen, fertility in dairy herds has declined. After calving, a high-yielding cow’s nutritional requirements rise rapidly with milk production, and she enters a period of negative energy balance that can last 10 to 12 weeks. This state is associated with a slower pulse frequency of luteinising hormone and low levels of glucose, insulin and insulin-like growth factor I, which together limit oestrogen production by the dominant follicle and delay the return to ovulation. It has also been linked to poorer oocyte quality, lower progesterone and lower pregnancy rates. These questions are explored further on the reproduction in farm animals page.

Programming the next generation

Nutrition also matters across generations. A large body of animal experiments and human epidemiology shows that conditions during early development influence the risk of chronic, non-communicable diseases such as type 2 diabetes and cardiovascular disease later in life. The field is known as the developmental origins of health and disease (DOHaD). Leading researchers in the field argue that much of this reflects normal developmental plasticity, in which the fetus adjusts to the signals it receives, with epigenetic mechanisms as one likely route. Evidence that some risk may pass through both maternal and paternal lines is being actively investigated.

What is established and what is still debated

• Established: severe undernutrition and weight loss can stop ovulation; leptin is one signal linking fat stores to the reproductive axis; suckling suppresses fertility through effects on GnRH secretion; obesity is associated with ovulatory problems and pregnancy complications; negative energy balance contributes to reduced fertility in high-yielding dairy cows.
• Still debated: how the many metabolic signals are combined in the brain; which effects of obesity are caused by weight itself rather than by associated conditions; how lactational signals reach GnRH neurons; and how far early-life programming and its possible transmission across generations apply to people.

The articles gathered under this topic span this whole history, from early descriptive studies of milk composition and lactational amenorrhoea to the metabolic and epigenetic research of recent decades.